In vivo, the transcription of the BLV genome in naturally infected lymphocytes is blocked by a specific protein that is consistently found in the plasma of BLV-infected cattle. The plasma BLV blocking (PBB) protein - which is not an interferon or an antibody molecule - most likely responsible for the fact that BLV infection in cattle is persistent despite a continuous and vigorous antiviral antibody response. We propose to study the regulatory role of the PBB protein in the spread of BLV infection in the animal and in BLV-induced leukemogenesis. These studies will be conducted in cattle naturally infected with BLV, having either high-risk or low-risk of developing leukemia. Such animals, which can be identified in our high-incidence leukemia study herd on the basis of pedigree data, will be compared longitudinally in regard to levels and fluctuations of the PBB protein, number of BLV infected cells in blood, size of a blastogenic BLV-specific lymphocyte subpopulation that could provide cells especially susceptible to neoplastic transformation, presence of persistent lymphocytosis, and titers of antiviral antibodies. Additional objectives of this proposal are to identify and isolate the cells that produce the PBB protein, and to prepare antibodies against this protein.